SG10202009354SA - Methods of preparing cytotoxic benzodiazepine derivatives - Google Patents

Methods of preparing cytotoxic benzodiazepine derivatives

Info

Publication number
SG10202009354SA
SG10202009354SA SG10202009354SA SG10202009354SA SG10202009354SA SG 10202009354S A SG10202009354S A SG 10202009354SA SG 10202009354S A SG10202009354S A SG 10202009354SA SG 10202009354S A SG10202009354S A SG 10202009354SA SG 10202009354S A SG10202009354S A SG 10202009354SA
Authority
SG
Singapore
Prior art keywords
methods
benzodiazepine derivatives
cytotoxic benzodiazepine
preparing cytotoxic
preparing
Prior art date
Application number
SG10202009354SA
Inventor
Baudouin Gérard
Manami Shizuka
Michael Louis Miller
Richard A Silva
Original Assignee
Immunogen Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Immunogen Inc filed Critical Immunogen Inc
Publication of SG10202009354SA publication Critical patent/SG10202009354SA/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06017Dipeptides with the first amino acid being neutral and aliphatic
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/55131,4-Benzodiazepines, e.g. diazepam or clozapine
    • A61K31/55171,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/26Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
    • C07C303/28Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/63Esters of sulfonic acids
    • C07C309/64Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
    • C07C309/65Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02Silicon compounds
    • C07F7/08Compounds having one or more C—Si linkages
    • C07F7/18Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804Compounds having Si-O-C linkages
    • C07F7/1872Preparation; Treatments not provided for in C07F7/20
    • C07F7/188Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08Tripeptides
    • C07K5/0802Tripeptides with the first amino acid being neutral
    • C07K5/0804Tripeptides with the first amino acid being neutral and aliphatic
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/55Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Pyridine Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
SG10202009354SA 2015-07-21 2016-07-21 Methods of preparing cytotoxic benzodiazepine derivatives SG10202009354SA (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562195023P 2015-07-21 2015-07-21
US201662327973P 2016-04-26 2016-04-26

Publications (1)

Publication Number Publication Date
SG10202009354SA true SG10202009354SA (en) 2020-11-27

Family

ID=56557925

Family Applications (2)

Application Number Title Priority Date Filing Date
SG10202009354SA SG10202009354SA (en) 2015-07-21 2016-07-21 Methods of preparing cytotoxic benzodiazepine derivatives
SG10202106529XA SG10202106529XA (en) 2015-07-21 2016-07-21 Methods of preparing cytotoxic benzodiazepine derivatives

Family Applications After (1)

Application Number Title Priority Date Filing Date
SG10202106529XA SG10202106529XA (en) 2015-07-21 2016-07-21 Methods of preparing cytotoxic benzodiazepine derivatives

Country Status (22)

Country Link
US (11) US10081640B2 (en)
EP (7) EP4286387A3 (en)
JP (8) JP6858745B2 (en)
KR (5) KR102660070B1 (en)
CN (5) CN113004288A (en)
AU (7) AU2016297608B2 (en)
CA (4) CA2992082A1 (en)
CY (2) CY1122553T1 (en)
DK (2) DK3325483T3 (en)
ES (4) ES2764548T3 (en)
HK (3) HK1252321A1 (en)
HR (1) HRP20201479T1 (en)
HU (1) HUE051541T2 (en)
IL (10) IL286788B2 (en)
LT (2) LT3325483T (en)
PL (2) PL3325482T3 (en)
PT (2) PT3325482T (en)
RS (2) RS59806B1 (en)
RU (3) RU2727151C2 (en)
SG (2) SG10202009354SA (en)
SI (2) SI3325482T1 (en)
WO (3) WO2017015495A1 (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113004288A (en) 2015-07-21 2021-06-22 伊缪诺金公司 Method for preparing cytotoxic benzodiazepine derivatives
KR102378167B1 (en) 2016-03-22 2022-03-23 에베 그룹 에. 탈너 게엠베하 Method and apparatus for bonding substrates
KR20240000650A (en) 2016-10-19 2024-01-02 인벤라 인코포레이티드 Antibody constructs
WO2018115485A1 (en) 2016-12-22 2018-06-28 Pierfrancesco Tassone A monoclonal antibody targeting a unique sialoglycosilated cancer-associated epitope of cd43
SG11201906666QA (en) 2017-01-25 2019-08-27 Immunogen Inc Methods of preparing cytotoxic benzodiazepine derivatives
CN113227127A (en) 2018-06-05 2021-08-06 伦敦大学国王学院 Delivering payload to gastrointestinal System BTNL3/8 targeting construct
CN113166053A (en) * 2018-11-12 2021-07-23 伊缪诺金公司 Method for preparing cytotoxic benzodiazepine derivatives
JP7437395B2 (en) * 2018-11-12 2024-02-22 イミュノジェン・インコーポレーテッド Method for preparing cytotoxic benzodiazepine derivatives
EP3947395A1 (en) * 2019-03-29 2022-02-09 ImmunoGen, Inc. Cytotoxic bis-benzodiazepine derivatives and conjugates thereof with cell-binding agents for inhibiting abnormal cell growth or for treating proliferative diseases

Family Cites Families (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3763183A (en) 1972-07-10 1973-10-02 Sterling Drug Inc 1,2,3,10,11,11a-hexahydro-5h-pyrrolo (2,1-c)(1,4)benzodiazepines
US3860600A (en) 1972-07-10 1975-01-14 Sterling Drug Inc Octahydropyrrido{8 2,1-c{9 {8 1,4{9 benzodiazepines
US4678784A (en) 1984-04-11 1987-07-07 Mcneilab, Inc. Method for the treatment of LHRH diseases and conditions
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
GB9205051D0 (en) 1992-03-09 1992-04-22 Cancer Res Campaign Tech Pyrrolobenzodiazepine derivatives,their preparation,and compositions containing them
EP0563475B1 (en) 1992-03-25 2000-05-31 Immunogen Inc Cell binding agent conjugates of derivatives of CC-1065
GB9818731D0 (en) 1998-08-27 1998-10-21 Univ Portsmouth Compounds
EP1109812B1 (en) 1998-08-27 2005-05-04 Spirogen Limited Pyrrolobenzodiazepines
JP2003514903A (en) 1999-11-24 2003-04-22 イムノージェン インコーポレーテッド Taxane-containing cytotoxic drugs and their therapeutic use
US6548042B2 (en) * 2000-08-07 2003-04-15 Arstad Erik Bis-phosphonate compounds
UA75093C2 (en) * 2000-10-06 2006-03-15 Dimensional Pharm Inc Aminopyridinyl-,aminoguanidinyl-, and alkoxyguanidinesubstituted phenylsubstituted phenylacetamides as protease inhibitors
US6441163B1 (en) 2001-05-31 2002-08-27 Immunogen, Inc. Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents
US6716821B2 (en) 2001-12-21 2004-04-06 Immunogen Inc. Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same
US6756397B2 (en) 2002-04-05 2004-06-29 Immunogen, Inc. Prodrugs of CC-1065 analogs
JP2005539009A (en) 2002-08-02 2005-12-22 イミュノジェン・インコーポレーテッド Cytotoxic substances including new potent taxanes and their therapeutic use
WO2004016801A2 (en) 2002-08-16 2004-02-26 Immunogen, Inc. Cross-linkers with high reactivity and solubility and their use in the preparation of conjugates for targeted delivery of small molecule drugs
RU2338747C2 (en) 2003-03-31 2008-11-20 Каунсил Оф Сайентифик Энд Индастриал Рисерч DIMERS OF PYRROL[2,1-c][1,4]BENZODIAZEPINE AS ANTITUMORAL AGENTS AND METHOD OF THEIR OBTAINING
EP1608663B1 (en) 2003-03-31 2008-11-05 Council of Scientific and Industrial Research Pyrrolo (2,1-c)(1,4) benzodiazepines dimers as antitumour agents and process thereof
RU2314309C2 (en) 2003-03-31 2008-01-10 Каунсил Оф Сайентифик Энд Индастриал Рисерч Pyrrolo[2.1-c][1.4]benzodiazepines, method for their preparing and pharmaceutical composition based on thereof
ATE421967T1 (en) 2003-03-31 2009-02-15 Council Scient Ind Res NON-CROSS-LINKING PYRROLOÄ2,1-CÜÄ1, 4ÜBENZODIAZEPINES AS POTENTIAL ANTITUMOR AGENTS AND THEIR PRODUCTION
US8088387B2 (en) 2003-10-10 2012-01-03 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
US7276497B2 (en) 2003-05-20 2007-10-02 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
EP1675857B1 (en) 2003-10-22 2011-07-13 THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES Pyrrolobenzodiazepine derivatives, compositions comprising the same and methods related thereto
JP4520411B2 (en) 2003-12-31 2010-08-04 カウンシル オブ サイエンティフィク アンド インダストリアル リサーチ Method for preparing pyrrolo [2,1-c] [1,4] benzodiazepine hybrid
PL1720881T3 (en) * 2004-03-01 2013-05-31 Medimmune Ltd 11-hydroxy-5h-pyrrolo[2,1-c][1,4]benzodiazepin-5-one derivatives as key intermediates for the preparation of c2 substituted pyrrolobenzodiazepins
GB0404578D0 (en) 2004-03-01 2004-04-07 Spirogen Ltd Pyrrolobenzodiazepines
GB0410725D0 (en) 2004-05-13 2004-06-16 Spirogen Ltd Pyrrolobenzodiazepine therapeutic agents
GB0412492D0 (en) * 2004-06-04 2004-07-07 Sterix Ltd Compound
GB0508084D0 (en) * 2005-04-21 2005-06-01 Spirogen Ltd Pyrrolobenzodiazepines
AU2006238686B2 (en) 2005-04-21 2011-10-06 Medimmune Limited Pyrrolobenzodiazepines
EP1931671B1 (en) 2005-10-05 2009-04-08 Spirogen Limited Alkyl 4- [4- (5-oxo-2, 3, 5, 11a-tetrahyd0-5h-pyrr0l0 [2, 1-c][1, 4]benzodiazepine-8-yloxy) -butyrylamino]-1h-pyrrole-2-carboxylate derivatives and related compounds for the treatment of a proliferative disease
JP2009521480A (en) * 2005-12-21 2009-06-04 アボット・ラボラトリーズ Antiviral compounds
ATE527262T1 (en) 2006-01-25 2011-10-15 Sanofi Sa NEW CYTOTOXIC AGENTS CONTAINING TOMAYMYCIN DERIVATIVES
US7465724B2 (en) 2006-02-13 2008-12-16 Council Of Scientific And Industrial Research Bis-pyrrolo[2,1-c][1,4]benzodiazepine-anthraquinone conjugates and a process for the preparation thereof
DK2446904T3 (en) 2006-05-30 2015-07-27 Genentech Inc The anti-CD22 antibodies, immunoconjugates and their uses thereof
PT2019104E (en) 2007-07-19 2013-12-03 Sanofi Sa Cytotoxic agents comprising new tomaymycin derivatives and their therapeutic use
ATE543826T1 (en) 2007-08-01 2012-02-15 Council Scient Ind Res PYRROLOÄ2,1-CUÄ1,4ÜBENZODIAZEPINE GLYCOSIDE-PRODRU S SUITABLE AS SELECTIVE ANTITUMOR AGENTS
JP2011523628A (en) 2008-04-30 2011-08-18 イミュノジェン・インコーポレーテッド Effective conjugates and hydrophilic linkers
PL2281006T3 (en) 2008-04-30 2018-01-31 Immunogen Inc Cross-linkers and their uses
GB0819095D0 (en) 2008-10-17 2008-11-26 Spirogen Ltd Pyrrolobenzodiazepines
GB0822260D0 (en) * 2008-12-05 2009-01-14 Merten Christoph Assay
EP2383263B1 (en) * 2008-12-30 2014-04-16 Industry-academic Cooperation Foundation, Chosun University Novel thiazolidinedione derivative and use thereof
US8426402B2 (en) 2009-02-05 2013-04-23 Immunogen, Inc. Benzodiazepine derivatives
IN2012DN02780A (en) 2009-10-06 2015-09-18 Immunogen Inc
US8314250B2 (en) * 2009-11-24 2012-11-20 Hoffmann-La Roche Inc. Sultam derivatives
WO2011071078A1 (en) * 2009-12-08 2011-06-16 国立大学法人岐阜大学 Aromatic compound, modification carrier that uses same and is used for synthesizing an oligonucleotide derivative, oligonucleotide derivative, and oligonucleotide construct
US8962279B2 (en) * 2009-12-30 2015-02-24 Intel Corporation Solid-phase chelators and electronic biosensors
RU2567753C2 (en) * 2010-02-11 2015-11-10 Селджин Корпорейшн Arylmethoxy isoindolin derivative, compositions including thereof and methods of their application
KR101637138B1 (en) 2010-02-24 2016-07-06 이뮤노젠 아이엔씨 Folate receptor 1 antibodies and immunoconjugates and uses thereof
MA34277B1 (en) 2010-04-15 2013-06-01 Spirogen Developments Sarl PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
EP2558475A1 (en) 2010-04-15 2013-02-20 Spirogen Sàrl Pyrrolobenzodiazepines used to treat proliferative diseases
WO2011130613A1 (en) 2010-04-15 2011-10-20 Seattle Genetics, Inc. Targeted pyrrolobenzodiazapine conjugates
MX343337B (en) 2011-02-15 2016-11-01 Immunogen Inc Methods of preparation of conjugates.
CN102234253B (en) * 2011-06-02 2013-07-03 重庆莱美药业股份有限公司 Method for preparing febuxostat intermediate
EP2887965A1 (en) * 2012-08-22 2015-07-01 ImmunoGen, Inc. Cytotoxic benzodiazepine derivatives
EP3722277A3 (en) * 2013-10-04 2021-01-20 Novartis AG 3'end caps for rna-interferring agents for use in rna
CN104628772A (en) * 2013-11-07 2015-05-20 四川恒康发展有限责任公司 Antitumor prodrug, activator, composition, and application thereof
CN103664896B (en) * 2013-11-25 2016-03-02 济南精合医药科技有限公司 A kind of synthetic process of crizotinib serving as antitumor molecular targeting medicament
TW201613930A (en) 2014-09-03 2016-04-16 Immunogen Inc Cytotoxic benzodiazepine derivatives
SI3189056T1 (en) * 2014-09-03 2020-10-30 Immunogen, Inc. Cytotoxic benzodiazepine derivatives
KR20240027148A (en) 2014-09-03 2024-02-29 이뮤노젠 아이엔씨 Conjugates comprising cell-binding agents and cytotoxic agents
CN113004288A (en) * 2015-07-21 2021-06-22 伊缪诺金公司 Method for preparing cytotoxic benzodiazepine derivatives
RS65120B1 (en) * 2015-11-25 2024-02-29 Immunogen Inc Pharmaceutical formulations and methods of use thereof

Also Published As

Publication number Publication date
US10899775B2 (en) 2021-01-26
US20190010169A1 (en) 2019-01-10
PL3325482T3 (en) 2021-01-11
SI3325482T1 (en) 2020-11-30
JP2023166434A (en) 2023-11-21
IL276631A (en) 2020-09-30
JP6995178B2 (en) 2022-02-21
WO2017015495A1 (en) 2017-01-26
IL276630B (en) 2021-06-30
CA2992082A1 (en) 2017-01-26
JP7337114B2 (en) 2023-09-01
HK1252322A1 (en) 2019-05-24
HK1252321A1 (en) 2019-05-24
EP4286387A3 (en) 2024-02-21
RS59806B1 (en) 2020-02-28
AU2021203148A1 (en) 2021-06-10
CY1123390T1 (en) 2022-03-24
SG10202106529XA (en) 2021-07-29
AU2023201339A1 (en) 2023-04-06
EP4163284A1 (en) 2023-04-12
IL276630A (en) 2020-09-30
US10787463B2 (en) 2020-09-29
PT3325482T (en) 2020-09-24
AU2023202221A1 (en) 2023-05-04
CN108055844A (en) 2018-05-18
EP3778602A1 (en) 2021-02-17
US11420982B2 (en) 2022-08-23
ES2959741T3 (en) 2024-02-28
JP2022046542A (en) 2022-03-23
AU2016297608A1 (en) 2018-02-08
CN108290895B (en) 2021-03-19
IL256860B (en) 2020-08-31
IL283355B (en) 2022-08-01
ES2933376T3 (en) 2023-02-06
KR102659706B1 (en) 2024-04-23
PL3325483T3 (en) 2020-05-18
EP3325482B1 (en) 2020-06-24
ES2764548T3 (en) 2020-06-03
JP2018522018A (en) 2018-08-09
EP3653628B1 (en) 2022-09-14
RU2018105609A (en) 2019-08-26
JP2023162264A (en) 2023-11-08
WO2017015502A1 (en) 2017-01-26
CN108026103A (en) 2018-05-11
US20170050986A1 (en) 2017-02-23
WO2017015496A1 (en) 2017-01-26
RU2018105756A3 (en) 2019-12-23
JP6858745B2 (en) 2021-04-14
US9890179B2 (en) 2018-02-13
CY1122553T1 (en) 2021-01-27
PT3325483T (en) 2020-01-15
CN113087763A (en) 2021-07-09
EP3325485A1 (en) 2018-05-30
HRP20201479T1 (en) 2020-12-11
AU2021202403A1 (en) 2021-05-20
US20180201626A1 (en) 2018-07-19
AU2016297087B2 (en) 2021-02-18
KR20180038460A (en) 2018-04-16
AU2021202403B2 (en) 2022-12-08
DK3325482T3 (en) 2020-09-28
IL294651B1 (en) 2023-10-01
ES2820358T3 (en) 2021-04-20
RU2746322C2 (en) 2021-04-12
KR20240055894A (en) 2024-04-29
US10370389B2 (en) 2019-08-06
US20170050985A1 (en) 2017-02-23
US20210171547A1 (en) 2021-06-10
EP3325485B1 (en) 2020-04-08
AU2016297607A1 (en) 2018-02-08
EP3778602B1 (en) 2023-07-12
US10081640B2 (en) 2018-09-25
IL305989A (en) 2023-11-01
IL286788B2 (en) 2024-01-01
US20230257400A1 (en) 2023-08-17
IL286788B1 (en) 2023-09-01
RU2018105752A3 (en) 2019-12-30
WO2017015502A8 (en) 2017-03-02
CN108290895A (en) 2018-07-17
IL256854A (en) 2018-03-29
RU2018105756A (en) 2019-08-21
JP2018526340A (en) 2018-09-13
AU2021203148B2 (en) 2023-01-12
IL294651B2 (en) 2024-02-01
EP3653628A1 (en) 2020-05-20
AU2016297608B2 (en) 2021-02-18
US20190389883A1 (en) 2019-12-26
RU2018105609A3 (en) 2020-04-30
IL256861B (en) 2020-08-31
AU2016297087A1 (en) 2018-02-08
SI3325483T1 (en) 2020-03-31
IL294651A (en) 2022-09-01
IL283355A (en) 2021-07-29
IL286788A (en) 2021-10-31
DK3325483T3 (en) 2020-01-20
KR102660070B1 (en) 2024-04-24
CA3227588A1 (en) 2017-01-26
US10392407B2 (en) 2019-08-27
KR20180038461A (en) 2018-04-16
JP2021035958A (en) 2021-03-04
US20190112320A1 (en) 2019-04-18
RU2727151C2 (en) 2020-07-21
JP2018524387A (en) 2018-08-30
US9873708B2 (en) 2018-01-23
CA2991305A1 (en) 2017-01-26
EP4286387A2 (en) 2023-12-06
JP2021100959A (en) 2021-07-08
CN108026103B (en) 2021-04-16
US20170051011A1 (en) 2017-02-23
IL256861A (en) 2018-03-29
HK1252323A1 (en) 2019-05-24
EP3325482A1 (en) 2018-05-30
EP3325483A1 (en) 2018-05-30
CA2991305C (en) 2024-03-12
HUE051541T2 (en) 2021-03-01
IL276631B (en) 2021-10-31
EP3325483B1 (en) 2019-10-02
CA2991326A1 (en) 2017-01-26
IL256860A (en) 2018-03-29
IL305279A (en) 2023-10-01
RS60840B1 (en) 2020-10-30
US20210171546A1 (en) 2021-06-10
CN113004288A (en) 2021-06-22
KR20240055903A (en) 2024-04-29
JP6787995B2 (en) 2020-11-18
LT3325482T (en) 2020-11-25
JP7334228B2 (en) 2023-08-28
US20200017526A1 (en) 2020-01-16
RU2018105752A (en) 2019-08-21
KR20180026741A (en) 2018-03-13
LT3325483T (en) 2020-01-27

Similar Documents

Publication Publication Date Title
IL291598A (en) Cytotoxic benzodiazepine derivatives
IL286788A (en) Methods of preparing cytotoxic benzodiazepine derivatives
IL287405A (en) Methods of preparing cytotoxic benzodiazepine derivatives
IL293192A (en) Methods of preparing indolinobenzodiazepine derivatives
HUP1400545A2 (en) Process for preparation of benzazepine derivatives
GB201513979D0 (en) Synthesis of benzodiazepine derivatives